The phenomenon of diffusion hypoxia is commonly believed to occur unless nitrous oxide-oxygen inhalation sedation is followed by  washout  with 100% oxygen for 5 minutes upon termination of the flow of nitrous oxide. When systematically studied, however, this phenomenon generally appears to be unfounded. The present study evaluated the effect of breathing room air instead of 100% oxygen in healthy (ASA 1) human volunteers following administration of sedative concentrations of nitrous oxide. The occurrence of hypoxia was determined objectively, using pulse oximetry and a standardized psychomotor skills test (Trieger test). Diffusion hypoxia was not observed using these criteria

Freels, Chris

Fuentes, Mike

Jeske, Arthur H

Whitmire, Clark W

PubMed

DigitalCommons@The Texas Medical Center

SCIENTIFIC REPORTNoninvasive Assessment of Diffusion HypoxiaFollowing Adnistration of Nitrous Oxide-OxygenArthur H. Jeske, DMD, PhD,*t Clark W. Whitmire, DMD, JD,t Chris Freels, DDS,t andMike Fuentes, DDS§*Department of Integrative Biology and Pharmacology, University of Texas Medical School-Houston, tDepartment of Oral andMaxillofacial Surgery and Anesthesiology, and tDepartment of Orthodontics, University of Texas Dental Branch-Houston,Houston, Texas; and §Department of Oral and Maxillofacial Surgery, Indiana University, Indianapolis, IndianaThe phenomenon of diffusion hypoxia is commonly believed to occur unless nitrousoxide-oxygen inhalation sedation is followed by "washout" with 100% oxygen for5 minutes upon termination of the flow of nitrous oxide. When systematically stud-ied, however, this phenomenon generally appears to be unfounded. The presentstudy evaluated the effect of breathing room air instead of 100% oxygen in healthy(ASA I) human volunteers following administration of sedative concentrations ofnitrous oxide. The occurrence of hypoxia was determined objectively, using pulseoximetry and a standardized psychomotor skills test (Trieger test). Diffusion hypoxiawas not observed using these criteria.Key Words: Nitrous oxide; Diffusion hypoxia.For decades, nitrous oxide-oxygen inhalation seda-tion has been used extensively in dentistry, with anexcellent safety record. Side effects associated with thissedative technique are minor, and reports of postseda-tion lethargy, nausea, and headache have been attribut-ed to a phenomenon known as "diffusion hypoxia.'1-3Standard teaching and practice has advocated for yearsthe routine administration of 100% oxygen to the pa-tient for 3-5 minutes following the administration of ni-trous oxide to counteract this effect.4 Diffusion hypoxiais postulated to occur at the end of inhalation sedation,when the flow of nitrous oxide is stopped. Due to itslow blood: gas solubility coefficient, nitrous oxide thendiffuses out of the blood in large volumes, diluting oxy-gen in lung alveoli and reducing alveolar oxygen ten-sion, which then produces hypoxia. This alveolar hyp-oxia may be manifested by clinical signs and symptomsof systemic hypoxia. The clinical significance of diffu-sion hypoxia came to be questioned in medical anesthe-siology studies done some time ago by Frumin and Edel-Received February 10, 2003; accepted for publication September1, 2003.Address correspondence to Dr Arthur Jeske, Department of Inte-grative Biology and Pharmacology, University of Texas-MedicalSchool, 6516 M.D. Anderson Boulevard, Houston, TX 77030; Ar-thur.H.Jeske@uth.tmc.edu.Anesth Prog 51:10-13 2004© 2004 by the American Dental Society of Anesthesiologyist5 and Stubbing and Sweeney,6 and more recently inthe dental outpatient setting.7,8 Nearly all of the medicalstudies that reported the occurrence of significant dif-fusion hypoxia following nitrous oxide administrationwere done in patients who had received a variety ofother anesthetic agents, including fixed intravenousagents, which may have contributed to a centrally me-diated, postoperative respiratory depression indepen-dent of any specific effect of nitrous oxide diffusion intothe alveoli. During nitrous oxide-oxygen conscious se-dation, no other sedatives are involved, although dentaloutpatients who have been administered other sedativesfrequently receive nitrous oxide and oxygen as an ad-ditional sedative modality.Practically, the routine administration of 100% oxy-gen following nitrous oxide-oxygen inhalation sedationprolongs the sedation procedure, and further contrib-utes to the drying of the respiratory tract that accom-panies this procedure. Although airway drying is notparticularly deleterious in healthy patients, the prolon-gation of patient chair time can cumulatively account fora significant amount of nonproductive time in the dentalclinic and the potentially unnecessary use of approxi-mately 30 L of oxygen in the average adult patient (6L/min flow rate for 5 minutes). Dunn-Russell et a17 de-termined by pulse oximetry that diffusion hypoxia wasISSN 0003-3006/04/$9.50SSDI 0003-3006(04)10Anesth Prog 51:10-13 2004not significant following nitrous oxide sedation in 24children, aged 41-113 months, based on the percentof hemoglobin oxygen saturation (SPO2) of arterial bloodduring the 5-minute postoperative period. Their subjectswere allowed to breathe room air following administra-tion of up to 40% nitrous oxide. Milles and Kohn8 stud-ied diffusion hypoxia in healthy adult dental patients anddemonstrated a statistically significant drop in the SPO2of 1.2%, but the slight hypoxia observed was not as-sociated with any adverse physiologic effects (no changein heart rate, respiratory rate, or systolic and diastolicblood pressure). More recently, Takarada et a19 reportedthat actual "clinical recovery time" (defined as the timefrom the end of dental surgery until the patient's leavingthe clinic) from nitrous oxide and oxygen inhalation se-dation averaged 40 minutes (ranging from 22 to 98minutes), although "recovery time" (defined as the timefrom the procedure until the patient was given permis-sion to leave the clinic) averaged 15 minutes (rangingfrom 5 to 35 minutes). This demonstrates the individualvariation of patient recovery from inhalation sedationand the potential need for even more objective tests ofrecovery from sedation.None of the studies done to date have reported theimpact on motor coordination of conditions that couldproduce significant diffusion hypoxia. In the presentstudy, we examine the effects of the inhalation of roomair in the postsedation period on the SPO2 and psycho-motor performance to evaluate the potential for diffu-sion hypoxia in the absence of 100% oxygen during therecovery period.METHODSEach experimental session began by seating the con-senting subject in a dental operatory at the Universityof Texas-Houston Dental Branch. The subject's healthhistory was briefly reviewed for contraindications to ni-trous oxide-oxygen inhalation sedation. Following as-sembly and check of the inhalation sedation apparatus,the subject was asked to complete a preoperative, writ-ten psychomotor skills test. 10 The score (number of dotsmissed on a connect-the-dot printed test) was recordedfor comparison with a second test. A pulse oximeterprobe was then attached to the subject's finger. Thepulse oximeter had been previously calibrated and pro-grammed to emit a visible and audible warning if he-moglobin oxygen saturation dropped below 90% and/or if the pulse rate dropped below 50 beats per minute(bpm) or rose above 120 bpm. The pulse oximeter uti-lized in this study was a Criticare Systems Inc model 507ER with integrated NIBP, pulse, and continuous-readpulse oximetry capability. The sedative procedure beganTable 1. Comparison of Percent Hemoglobin Oxygen Satu-ration in the 2 Experimental Groups During Recovery Period(+SEM)*Time 100% °2 Recoveryt Room Air Recovery$0 s 99.769 ± 0.166 99.962 ± 0.17530 s 99.769 ± 0.175 99.153 ± 0.3371 min 99.692 ± 0.175 99.230 + 0.7561.5 min 99.846 ± 0.077 99.076 ± 1.1122 min 99.538 ± 0.183 98.384 ± 0.4292.5 min 99.769 ± 0.166 98.461 + 0.4623 min 99.461 ± 0.183 98.615 ± 0.6193.5 min 99.462 ± 0.183 98.615 ± 0.4014 min 99.384 ± 0.311 98.615 ± 0.3694.5 min 99.153 ± 0.191 98.538 + 0.4625 min 99.615 ± 0.180 98.385 ± 0.432tn = 13.*n = 14.* No significant differences were detected at P < .05, Stu-dent's t test.by setting the flow of oxygen through the nasal hood at5-6 L/min; the nasal hood, with oxygen flowing, wasthen placed comfortably over the subject's nose, takingcare to avoid leakage of the gases from the peripheryof the nasal hood. The subjects were asked to breatheonly through their nose, during which the flow of oxy-gen was matched to the subjects' minute respiratory vol-ume in liters per minute.After the basal flow rate of oxygen had been deter-mined, sedation began by reducing oxygen flow andadding nitrous oxide as the balance of the total flow, toproduce an initial gas mixture of 20% nitrous oxide and80% oxygen. Following a 1- to 2-minute equilibrationperiod, the concentration of nitrous oxide was increasedin increments of 10% each minute, until the subject re-ported symptoms of sedation (eg, warmth, tingling, cir-cumoral numbness, etc) and/or a subjective feeling ofrelaxation (anxiety relief), which was obtained at a min-imum nitrous oxide concentration of 35-40%. The sub-jects were maintained at this final nitrous oxide concen-tration for 10-15 minutes. Thirteen subjects were ran-domly chosen to recover at the end of the sedative pe-riod by breathing room air (without the nasal hood inplace), and the remaining 14 subjects were allowed torecover by breathing 100% oxygen for 5 minutesthrough the nasal hood. During the recovery period, ox-ygen saturation values were recorded every 30 secondsfor 5 minutes. At the end of the 5-minute recovery pe-riod, a motor coordination test was administered forcomparison with the preoperative one, and the testscore was recorded.Pre- and postsedation Sp02 values and psychomotorskill test scores were compared between groups usingStudent's non-paired t-test, P < .05 significance. TheJeske et al 1112 Assessment of Diffusion HypoxiaTable 2. Trieger Test Scores for the 2 Experimental Groups (Reported As Dots Missed;+SEM)*100% Oxygen Recovery Groupt Room Air Recovery Group+Preoperative scores: 5.154 ± 1.285 3.923 ± 0.923Postoperative scores: 4.692 ± 1.237 2.769 + 0.752t n = 13.* n = 14.* No significant differences detected at P < .05, Student's t test.subjects in the study were recruited from the third-yearpredoctoral dental class, all of whom were trained in theadministration of nitrous oxide and oxygen in a labo-ratory, which is required as part of their sedation train-ing course. Since these students are all part of a groupthat undergoes nitrous oxide sedation, recruitment con-sisted of making an announcement in class that subjectswere needed, with assurance that their decision to par-ticipate or not to participate in the study had no impacton their course grade (the laboratory is ordinarily notgraded, but participation is required for all students forreceipt of a final grade in the course). This populationwas deemed suitable for the proposed study because anapproximately equal number of male and female stu-dents were in the class, were closely age-matched, werehealthy adults, and had a professional interest in theimplications of the study. Inclusion criteria for the sub-jects consisted of a willingness to participate, healthyphysical (ASA I) status, and a lack of any contraindica-tions to administration of nitrous oxide and oxygen. Ex-clusion criteria included lack of willingness to partici-pate; chronic upper airway disease; upper airway infec-tions and inflammation; pregnancy; and intolerance tothe apparatus, including latex allergy and claustrophobicfear of the nasal hood ("mask").The study was a noncrossover design because the stu-dents who were potential subjects were only required toparticipate in 1 session of nitrous oxide-oxygen seda-tion, and the study was neither double- nor single-blind-ed because the subjects, by way of their prerequisite lec-tures, have intimate knowledge of inhalation sedationand diffusion hypoxia and its physiologic etiology. Be-cause of this limitation, only parametric measures of dif-fusion hypoxia (eg, Sp02, other vital signs, and an ob-jectively measured motor coordination test) were mea-sured as outcome criteria. The control group in thisstudy was the group that received 100% oxygen via thenasal hood for 5 minutes immediately following admin-istration of nitrous oxide and oxygen at a sedative con-centration. This study was approved by the Universityof Texas-Houston Health Science Center's Committeefor the Protection of Human Subjects as protocol HSC-DB-00-015.RESULTSAs shown in Table 1, at no time did any subject expe-rience clinical hypoxia as assessed by pulse oximetry,nor were there any statistically significant differences be-tween the groups at any measurement time up to 5 min-utes after the cessation of the flow of nitrous oxide andoxygen.Results of the postsedation psychomotor skills test aresummarized in Table 2. Surprisingly, there was actuallya slightly poorer performance on this test in the control(100% oxygen recovery) group versus the room-air re-covery group, although the difference was not statisti-cally significant. Our study did not identify a significantbasis for this difference.Although the data are not directly reported, therewere no clinically significant changes in heart rate, bloodpressure, or respiratory rate in any of the subjects atany time.DISCUSSIONThis study did not identify diffusion hypoxia in normal,healthy (ASA I) human subjects while being adminis-tered room air in the immediate postsedation period fol-lowing equilibration with a minimum of 35% nitrous ox-ide for 10 minutes. This observation was based on pulseoximetry and an objective psychomotor skills (Trieger)test to assess recovery. There were no clinically or sta-tistically significant differences between the room air-recovery group and a control group that was adminis-tered 100% oxygen, suggesting that recovery with roomair instead of 100% oxygen does not result in signs ofmotor coordination and/or changes in Sp02 values at-tributable to diffusion hypoxia. Although values are notreported here, blood pressure, heart rate, and respira-tory rate remained normal in both groups during seda-tion with nitrous oxide and in the postsedation recoveryperiod. Three weaknesses of the present study are that(a) it involved only ASA I subjects who were not selectedfor administration of nitrous oxide based on preopera-tive anxiety; (b) it did not utilize high (65-70%) nitrousAnesth Prog 51:10-13 2004Anesth Prog 51:10-13 2004 Jeske et al 13oxide levels; and (c) it did not confirm SPO2 values bymeasurement of arterial oxygen saturation. However,the findings are consistent with reports from the medicalliterature. For example, in a study on general anesthe-sia, patients who were equilibrated for 45 minutes to 1hour with 79% nitrous oxide and 21% oxygen did notexhibit significant hemoglobin desaturation when sud-denly switched to room air.1' Additional studies areneeded to establish the impact of room-air recoveryfrom nitrous oxide sedation on ASA II and ASA III pa-tients, especially those with compromised pulmonaryand cardiovascular function. Assessment of complete re-covery from nitrous oxide-oxygen inhalation sedationshould ideally utilize both objective measures and theclinical judgment of the operator, and 100% oxygenshould be administered to any patient who exhibits ad-verse signs and/or symptoms during inhalation seda-tion, including hypoxia in the immediate postsedationperiod.ACKNOWLEDGMENTSThe authors express their thanks to the members of theUniversity of Texas Dental Branch Class of 2002 fortheir willing participation in this study.REFERENCES1. Fink BR. Diffusion anoxia. Anesthesiology. 1955;16:511-519.2. Fanning GL, Colgan FJ. Diffusion hypoxia following ni-trous oxide anesthesia. Anesth Analg Curr Res. 1971;50:86-91.3. Stewart RD, Goralyeb MJ, Pelton GH. Arterial bloodgases before, during and after nitrous oxide: oxygen adminis-tration. Ann Emerg Med. 1986:15:1177-1180.4. Malamed SF. Sedation: A Guide to Patient Manage-ment. 4th ed. St Louis: Mosby; 2003:199-200.5. Frumin MJ, Edelist G. Diffusion anoxia: a critical re-appraisal. Anesthesiology. 1969;31 :243-249.6. Stubbing JF, Sweeney BP. Diffusion hypoxia: does itexist? Can J Anesth. 1989;36:S67-S68.7. Dunn-Russell T, Adair SM, Sams DR, Russell CM, Bar-eni JT. Oxygen saturation and diffusion hypoxia in childrenfollowing nitrous oxide sedation. Pediatr Dent. 1993:16:88-92.8. Milles M, Kohn G. Nitrous oxide sedation does notcause diffusion hypoxia in healthy patients [abstract]. J DentRes. 1999;78:1627S.9. Takarada T, Kawahara M, Irifune M, et al. Clinical re-covery time from conscious sedation for dental outpatients.Anesth Prog. 2002;49:124-127.10. Newman MG, Trieger NT, Miller JC. Measuring recov-ery from anesthesia-a simple test. Anesth Analg. 1969;48:136-140.11. Selim D, Markello R, Baker JM. The relationship ofventilation to diffusion hypoxia. Anesth Anaig Curr Res.1970;49:437-440.

Noninvasive assessment of diffusion hypoxia following administration of nitrous oxide-oxygen

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Noninvasive assessment of diffusion hypoxia following administration of nitrous oxide-oxygen.

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Noninvasive assessment of diffusion hypoxia following administration of nitrous oxide-oxygen.

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